Faculty Profile: Ashani Weeraratna, Ph.D.

Faculty Profile: Ashani Weeraratna, Ph.D.

Focus Magazine recently spoke with Ashani Weeraratna, Ph.D., associate professor in Wistar’s Tumor Microenvironment and Metastasis program. She joined Wistar in 2011 from the National Institutes of Health and her research interests include melanoma and the relationship between cancer and aging.

Focus: What brought you to The Wistar Institute?

I chose to come because Wistar has one of the world’s foremost melanoma programs, which is led by Meenhard Herlyn. I love that the Institute has such a large focus on basic cancer research, but it is also affiliated with some nearby, very prestigious hospitals. In keeping with this, I was also very attracted by the fact that the Cancer Center director, Dario Altieri, is really trying to push forward a program of cancer therapy and making a translational bridge between basic research and clinical cancer research.

Speaking of creating a bridge, your line of work bridges melanoma and aging. How are the two related?

I think melanoma is often perceived as a disease of younger people, but that is just not true. It turns out the overall incidence of melanoma is 21 per 100,000, but in patients over 65, it jumps to 69 per 100,000. In addition to having a higher incidence of melanoma, older people also have much poorer prognoses. We have been interested in why that is, so we’ve been looking at changes in the aging microenvironment that might initiate tumor progression.

What do you mean by aging microenvironment?

The aging microenvironment essentially means what is going on in your body in the absence of any tumor whatsoever. A good example is your skin. It turns out that up to 15 percent of the fibroblasts, a type of cell in your skin, start to undergo changes that make them look old, which is a process we call senescence. When that happens, those cells secrete all sorts of factors, like chemokines and cytokines, which are different factors that encourage growth, and have recently been shown to promote tumor progression. Those senescing cells are also associated with chronic inflammation throughout the body, and these inflammatory factors may promote tumor progression. What we find is that if you take a tumor and put it in a “young” microenvironment you see it behave differently versus its behavior in an “old” microenvironment. In the older microenvironment, we see an increase in progression in the exact same tumor cells. So it tells us that something is going on in older non-malignant cells that can either actively promote or permit—we are not exactly sure which yet—the progression of tumors.

Now, what is the difference between the aging microenvironment in cancer versus tumor microenvironment?

The tumor microenvironment is essentially what is going on in the vicinity of the tumor. You have fibroblasts that might support the tumor cells, or new blood vessels that feed the tumor, and there are a host of immune cells attracted to the tumor site as well. Essentially, you find a whole bunch of cells that can support a tumor as well as attack it, and understanding this, and how to target these microenvironmental factors is critical for being able to tailor safe and effective therapies in order to halt tumor progression.

And when you say “progression” you are talking about the spread of tumors, correct?

We look at what molecular steps occur as a tumor invades from the skin and into the body, and how we can reverse that. We look at different signaling pathways that work in both development of the organism and tumor growth. So I work on the Wnt signaling pathway, and we found that Wnt [family of genes] can promote both the growth of melanoma and the invasion of the tumor into the rest of the body.

Does the Wnt pathway open a strategy for a possible therapeutic intervention?

So it turns out that the Wnt pathway signals are transduced by a series of tyrosine kinase receptors on the cell surface, and we’re interested in one called ROR2. Kinases and their receptors are great targets for inhibitors, as you can see with recent trials of BRAF inhibitors for melanoma, which are inhibitors of the mutant BRAF kinase.

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Featured Image: Horner Brass Microscope

The microscope in the image belonged to William E. Horner, M.D., a collaborator with Caspar Wistar, M.D., in the early 1800s.

Dr. Horner, a lecturer at the University of Pennsylvania, was a pioneer of the use of microscopes in anatomical and medical research. He authored Special Anatomy and Histology, a seminal text on the subject.